The objective of this research project is to test the hypothesis that capillary hydrostatic pressure (Pc) is regulated during changes in arterial and venous pressures. Previous estimates of capillary pressure and of pre- and postcapillary resistance in whole-organ preparations indicate a tendency for Pc to be regulated in some tissues, but these studies are limited by several critical assumptions that may consistently result in overestimating the extent to which Pc is controlled. The few microcirculatory studies which have examined this question have been performed primarily on the intestine, with quite variable results, presumably because normal vascular tone and blood flow regulation were severly compromised. Direct measurements of capillary pressure and other microvessel pressures will be made with a servo-null micropressure system while local arterial and venous pressures are varied. The experiments will be conducted in three stages. First, the intravascular pressure distribution in the entire microcirculation will be measured as arterial pressure (Pa) is lowered, and as Pa and venous pressure are raised. Possible disruption of normal control mechanisms by micropressure pipettes will be evaluated. Second, blood flow to portions of the microvascular network will be measured simultaneously with downstream capillary pressures while lowering Pa in order to determine the extent to which Pc regulation is coupled to regulation of blood flow. Third, the vascular site(s) of possible Pc control will be identified by quantitating changes in microvessel diameters, red-cell velocities, and calculated volume flows for each vascular branching order. Absolute and relative microvascular resistances will be determined during arterial and venous pressure changes using three different methods. These experiments will be conducted in cheek pouch, mesentery, and skeletal muscle micrecirculations of anesthetized hamsters, and in the cutaneous circulation of unanesthetized bats in order to determine possible variations in capillary pressure regulation among different tissues. If Pc is not regulated under these conditions, the results will have important implications about control of interstitial volume during increased gravitational loads and during arterial hypo- and hypertension.